A better understanding of metabolic disorders which affect the nervous system is the goal of this project. In some phases, the studies are purely diagnostic and are applied to assist in identifying the less common or new disorders of metabolism. Other phases deal with biochemical observations in known disorders and are designed to elucidate the pathogenesis of the disease. In some poorly understood groups of neurologic disease, studies are conducted to draw biochemical correlations where none had previously been known or were poorly developed. Morphologic correlation is made by light microscopic and ultrastructural studies. Therapeutic trials are conducted in selected disorders. Disorders studied include the lysosomal storage diseases, the leukodystrophies, spinocerebellar degenerations, and amino-acidopathies.